Relationship of APOE, age at onset, amyloid and clinical phenotype in Alzheimer disease

The Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review


The apolipoprotein E (APOE) ε4 allele is the most well-established risk factor for Alzheimer's disease (AD), although its relationship to age at onset and clinical phenotype is unclear. We aimed to assess relationships between APOE genotype and age at onset, amyloid-beta (Aβ) deposition and typical versus atypical clinical presentations in AD. Frequency of APOE ε4 carriers by age at onset was assessed in 447 AD patients, 138 atypical AD patients recruited by the Neurodegenerative Research Group at Mayo Clinic, and 309 with typical AD from ADNI. APOE ε4 frequency increased with age at onset in atypical AD but showed a bell-shaped curve in typical AD where highest frequencies were observed between 65 and 70 years. Typical AD showed higher APOE ε4 frequencies than atypical AD only between the ages of 57 and 69 years. Global Aβ standard uptake value ratios did not differ according to APOE e4 status in either group. APOE genotype varies by both age at onset and clinical phenotype in AD, highlighting the heterogeneous nature of AD.

Original languageEnglish (US)
Pages (from-to)90-98
Number of pages9
JournalNeurobiology of aging
StatePublished - Dec 2021


  • Apolipoprotein
  • Atypical Alzheimer's disease
  • Beta-amyloid, PET
  • Logopenic
  • Posterior cortical atrophy

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology


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